Clinical Trials

Inclusion Criteria:

Each patient must meet the following criteria to be enrolled in PK Run-in Cohort or the Treatment Cohort of this study:

• Female sex assigned at birth.
• ≥ 18 years of age.
• Not lactating, pregnant, or planning to become pregnant in the next year and agrees to take adequate steps to prevent becoming pregnant 7 days before beginning treatment, during treatment and for 9 months after last dose and not breast feeding during treatment and for 3 months after last dose.
• Must agree to one non-hormonal highly effective method of contraception for the entire duration of study participation. Highly effective methods of birth control are defined as those, alone or in combination, that resulted in a low failure rate of < 1% per year when used consistently and correctly such as intrauterine devices (IUDs, non-hormonal such as copper IUD), sexual abstinence or vasectomized partner. Barrier contraceptives (e.g., male condom or diaphragm) are acceptable if used in combination with spermicides (e.g., foam, gel).
• Premenopausal defined as any female who has experienced menarche and does not meet any of the following criteria for postmenopausal:
  • Permanently sterilized (e.g., tubal occlusion, hysterectomy, bilateral oophorectomy, or bilateral salpingectomy); or
  • Amenorrheic for 12 or more months; or
  • Amenorrheic for < 12 or more months and follicle-stimulating hormone (FSH) or plasma estradiol are in the postmenopausal range.
• Pathologic confirmation of strongly estrogen receptor positive (ER+) (defined as estrogen receptor [ER] ≥ 67% or Allred Score 6-8) by local institution protocol.
• Eastern Cooperative Oncology Group ECOG Performance Status (ECOG PS) of 0 to 2.
• Nottingham Grade 1 or 2.
• HER2- breast cancer (histologically confirmed) using American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines defined as one of the following:
  • 0 or 1+ by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) not done;
  • 0 or 1+ by IHC and not amplified by FISH;
  • 2+ by immunohistochemistry with average of < 4.0 HER2 signals per cell and an HER2/CEP17 ratio ≥ 2.0;
  • 2+ by immunohistochemistry with average of ≥ 4.0 and < 6.0 HER2 signals per cell and an HER2/CEP17 ratio < 2.0;
  • IHC not done and not amplified by fluorescence in situ hybridization (FISH).
• Clinical Stage IIA or IIB invasive breast cancer (per American Joint Committee on Cancer [AJCC] 8th edition clinical staging) see Appendix 10.
• Largest tumor diameter2.0 cm either by imaging or clinical examination.
• Magnetic resonance imaging (MRI) ≤ 30 days of registration.
• Mammogram performed ≤ 90 days of registration (Treatment Cohort only).
• Must have given written informed consent before any study-related activities are carried out and must be able to understand the full nature and purpose of the trial, including possible risks and adverse effects.
• Willing to provide tissue samples for research purposes.

Exclusion Criteria: 

Subjects who meet any of the following criteria will be excluded from the PK Run-in Cohort and the Treatment Cohort:

• Inflammatory breast cancer defined as clinically significant erythema of the breast and/or documented dermal lymphatic invasion.
• Any prior diagnosis or treatment for breast cancer, including carcinoma in situ, or history of any other active malignancy within the past 2 years prior to study entry, with the exception of:
  • Adequately treated in situ carcinoma of the cervix uteri;
  • Adequately treated basal cell carcinoma or localized squamous cell carcinoma of the skin;
  • Any other malignancy with a life expectancy of more than 2 years.
• Any uncontrolled intercurrent illness including, but not limited to:
  • Ongoing or active infection requiring systemic treatment with strong inhibitors/inducers of CYP450 enzymes (including bacterial infection, fungal infection, or detectable viral infection).;
  • Symptomatic congestive heart failure;
  • Unstable angina pectoris;
  • Uncontrolled symptomatic cardiac arrhythmias;
  • Uncontrolled hypertension (defined as blood pressure > 160/90 mm Hg);
  • Uncontrolled diabetes (Hemoglobin A1c [HbA1c] > 50 mmol/mol);
  • Marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a QTc interval > 470 milliseconds [msec]) using Fridericia’s QT correction formula seen ≤ 28 days of registration.
• Any of the following co-morbid conditions:
  • Known cataracts or retinopathy;
  • History of deep vein thrombosis (DVT)/pulmonary embolism (PE);
  • Known activated protein C (APC) resistance, an inherited coagulation disorder.
• Evidence of the following laboratory abnormalities ≤ 28 days prior to registration:
  • Creatine clearance < 60 ml/hr by the Cockcroft-Gault equation;
  • Total bilirubin ≥ 1.5 x upper limit of normal (ULN);
  • Aspartate aminotransferase (AST) or alanine amino transferase (ALT) ≥ 2.5 x ULN;
  • Platelet count (PLT) ≤ 75,000/mm^3 ;
  • Hemoglobin (Hb) ≤ 10 g/dL.
• Hormonal therapies including birth control and hormone replacement therapy during the study or within 1 week of registration.
• Allergy to endoxifen, goserelin, or exemestane or any of their components.
• Participation in another investigational clinical trial ≤ 6 months of registration.
• Not willing or able to understand the study information and/or informed consent.

Note: Other protocol defined Inclusion/Exclusion Criteria may apply.

Eligibility last updated 11/7/22. Questions regarding updates should be directed to the study team contact.